Blood nerve barrier permeability to ions and nonelectrolytes is very low, indicating limited exchange between plasma and nerve endoneurium. The nerve barrier does not have a regulatory transport system for calcium. As a result, nerve calcium concentration varies directly with plasma calcium concentration. The integrity of the blood-nerve barrier to small nonelectryolytes is maintained with age in the rat. The blood-nerve barrier has carriers for the transfer of manganese and of neutral amino acids between plasma and nerve, both of which are required for nerve function. In addition, cationized albumin is taken up into the nerve at a greater rate than native albumin, by receptor-mediated transcytosis. Permeabilities of both nerve capillaries and perineurium increase during the first few weeks of Wallerian degeneration. Nerve capillary permeability eventually returns to normal, but perineurial permeability remains elevated, suggesting that nerve fibers are required to maintain perineurial nerve barrier integrity.